Diagnosis

After asking the patient’s medical history and a thorough physical examination, further steps in the diagnosis of hemophilia follow: In 2/3 of the cases there are cases of haemophilia in the family, which is why it is necessary to ask about a family history of the disease when the patient presents himself to the doctor with symptoms suspected of haemophilia. Patients report bruising as a result of even the smallest injuries. The severity of the haemophilia disease is differentiated into a mild, moderate or severe form of the disease.

The examination of a blood sample provides the following results, typical for haemophilia: The bleeding time is normal (= primary coagulation is intact), but the function of plasmatic coagulation is reduced, which is why the so-called PTT time is prolonged. PTT stands for the partial thromboplastin time. It is measured in laboratory chemical tests to check the function of factors I, II, V, VIII to XII and XIV and XV.

Since one factor of the coagulation cascade is missing in haemophilia, the coagulation cascade cannot run optimally, resulting in a prolonged coagulation time. In order to be able to differentiate between haemophilia A and B, the patient’s blood must be examined for factors VIII and IX. The missing factor determines the form of the haemophilia disease.

Differential diagnosis

Haemophilia must be distinguished from other disorders of the coagulation system, in particular von Willebrand- syndrome. The von Willebrand factor (vWF) acts together with factor VIII-C in the factor VIII complex and causes the inhibition of premature factor VIII degradation. In addition, the factor promotes coagulation by mediating platelet adhesion at the injured vascular site.

Thus vWF is an important component of both primary and secondary coagulation. If von Willebrand- syndrome is present, the formation of vWF in the cells of the vascular wall takes place only to a small extent or in a defective manner. The reduced rate of formation or inadequate function of the von Willebrand factor is due to mutations of the gene for factor formation.

The syndrome or the causative gene mutation is inherited in an autosomal dominant manner: the genetic information for vWF is located on chromosome number 12, which is not a sex chromosome. In dominant inheritance, a diseased allele suppresses the effect of the second, healthy allele, so that the disease is already caused by the mutation of one gene and causes clinical symptoms. Patients typically suffer from skin and mucosal bleeding, less from spontaneously occurring bleeding like haemophilia patients.

The disease often only becomes apparent when prolonged bleeding occurs after surgery. The bleeding time of patients after an injury is prolonged and also the values of plasmatic coagulation are pathologically altered (prolonged PTT). von Willebrand and syndrome is treated with desmopressin or the replacement of factor VIII and vWF to stabilise the coagulation (for further explanation see “Therapy of haemophilia”).

The symptoms of the forms of haemophilia do not differ:

The haemophilia disease normally only leads to clinical symptoms in men. – The bleeding disorder causes excessive bleeding that is not in proportion to the preceding, usually banal accident (trauma). The bleeding time is normal, but typically there is secondary bleeding that does not occur in healthy people.
There are three different types of haemophilia, which are defined by the residual activity of the affected coagulation factors: 1. severe haemophilia (haemophilia) with less than 1% residual activity or still existing part of the functional factor, in which spontaneous bleeding occurs and joint bleeding occurs 2. moderate haemophilia (haemophilia) with factor activity between 1 and 5% of normal factor activity and the occurrence of bruises (= haematomas) after slight trauma 3. slight haemophilia (haemophilia) with 5-15% residual activity and in which patients report symptoms such as haematomas (bruising) after significant trauma and post-operative bleeding. – Women who usually only have altered genetic information for the haemophilia usually show no clinical symptoms with over 50% residual activity. – Patients suffer from bleeding into large joints such as the knee, hip or shoulder joint, which is referred to as haemarthrosis.

The bleeding triggers an inflammatory reaction with repair processes in the joint, which can lead to stiffening of the joint. – In addition, bleeding can occur in the muscles and soft tissue. The bleeding leads to an increase in pressure in the muscles or tissue, as there is now more volume available.

This can lead to compartment syndrome, especially in the arms and legs: The increased pressure causes the compression of vessels and nerves, so that the extremities are undersupplied and large areas of tissue can die. Compartment syndrome must be treated by the surgeon as soon as possible to prevent the loss of the limb. – Bleeding into the abdomen occurs, which is a life-threatening situation for the patient.

After operations, unusually long bleedings are possible. In addition, there may be long periods with blood in the urine. This can lead to anaemia, as the patient constantly loses blood, possibly unnoticed.
Cerebral haemorrhages (= intracranial haemorrhages) are particularly dangerous, as they lead to death in 10% of patients suffering from haemophilia. Bleeding should be avoided at all costs in haemophiliacs, which is why the patient should not be given medication that inhibits blood clotting, such as acetylsalicylic acid (Aspirin®), and intramuscular injections (=injections into the muscles) should not be given. If trauma with bleeding occurs, careful local haemostasis is of great importance to prevent bleeding into neighbouring tissues.

The drug therapy of hemophilia consists of the replacement of coagulation factors which the body itself cannot produce in sufficient quantities. Patients with a mild hemophilia receive the coagulation factor preparations as required, i.e. when trauma with bleeding has occurred or when a major operation is planned, after which there may be severe bleeding. In patients with moderate to severe hemophilia, prophylactic factor replacement should be performed, i.e. the missing factor should be given permanently before bleeding occurs.

If there is a residual activity of factor VIII of more than 15% or factor IX of more than 20-25%, no regular therapy is necessary; these patients receive the missing coagulation factor in case of spontaneous bleeding or before planned operations. Especially the permanent therapy as well as the therapy before surgery can be done in the form of a home self-treatment, where the patient applies the missing coagulation factor himself. For patients with the mild form of hemophilia there is an alternative therapy: The active ingredient desmopressin (e.g. Minirin®) leads to a release of factor VIII, which is stored in the vessel walls.

However, the drug can only be administered for a few days at a time, as the storage capacity in the vessel walls is exhausted after stimulation of factor release and has to be replenished. There are three options for intervention in acute therapy of hemophilia:

The patient receives activated prothrombin, a substance that promotes blood clotting, so that the bleeding is stopped as quickly as possible. – Another therapeutic option is the administration of factor VII preparations. This factor is at the beginning of the coagulation cascade and initiates its regular course. – The third therapeutic option is the administration of animal Factor VIII-C to enable hemostasis in the patient.